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Generation of a novel, cyclooxygenase-2–targeted, interferon-expressing, conditionally replicative adenovirus for pancreatic cancer therapy
- Source :
- The American Journal of Surgery. 204:741-750
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Background Oncolytic adenoviruses provide a promising alternative for cancer treatment. Recently, adjuvant interferon (IFN)-alfa has shown significant survival benefits for pancreatic cancer, yet was impeded by systemic toxicity. To circumvent these problems adenovirus with high-level targeted IFN-alfa expression can be generated. Methods Conditionally replicative adenoviruses (CRAds) with improved virulence and selectivity for pancreatic cancer were generated. The vectors were tested in vitro, in vivo, and in human pancreatic cancer and normal tissue specimens. Results Adenoviral death protein and fiber modifications significantly improved oncolysis. CRAds selectively replicated in vitro, in vivo and showed persistent spread in cancer xenografts. They showed high-level replication in human pancreatic cancer specimens, but not in normal tissues. Improved IFN-CRAd oncolytic efficiency was shown. Conclusions Optimized cyclooxygenase-2 CRAds show highly favorable effects in vitro and in vivo. We report a pancreatic cancer–specific, highly virulent, IFN-expressing CRAd, and we believe that adenovirus-based IFN therapy offers a new treatment opportunity for pancreatic cancer patients.
- Subjects :
- Genetic enhancement
Mice, Nude
Alpha interferon
Virus Replication
medicine.disease_cause
Article
Adenoviridae
Mice
In vivo
Cell Line, Tumor
Pancreatic cancer
Adenovirus E3 Proteins
Biomarkers, Tumor
medicine
Animals
Humans
Interferon alfa
Oncolytic Virotherapy
business.industry
Gene Transfer Techniques
Interferon-alpha
Cancer
General Medicine
medicine.disease
Xenograft Model Antitumor Assays
Virology
Oncolytic virus
Pancreatic Neoplasms
Cyclooxygenase 2
Cancer research
Female
Surgery
business
Carcinoma, Pancreatic Ductal
medicine.drug
Subjects
Details
- ISSN :
- 00029610
- Volume :
- 204
- Database :
- OpenAIRE
- Journal :
- The American Journal of Surgery
- Accession number :
- edsair.doi.dedup.....abe744253979c99caec2b25590acf210